Urea
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
- Urea
- Urea: From Dermatitis-Type Skin Conditions to Dermatitis (Radiation- and Drug-Induced Settings)
Urea: From Dermatitis-Type Skin Conditions to Dermatitis (Radiation- and Drug-Induced Settings)
One-Sentence Summary
Urea is a topical humectant and keratolytic agent, originally used for skin conditions such as atopic eczema, contact dermatitis, seborrheic dermatitis and seborrheic keratosis. The TxGNN model predicts it may be effective for dermatitis, with 10 clinical trials and 20 publications currently supporting this direction. Much of this prediction overlaps with existing uses, and the newer signals are prevention and treatment of radiodermatitis and capecitabine-associated hand-foot skin reactions.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Atopic eczema, contact dermatitis, seborrheic dermatitis, seborrheic keratosis and related skin conditions (knowledge-graph indications; no approved indication text in the Singapore licences) |
| Predicted New Indication | Dermatitis |
| TxGNN Prediction Score | 98.21% |
| Evidence Level | L2 (see note below) |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 4 |
| Recommended Decision | Proceed with Guardrails |
Note on evidence level: The data compiled for this report assigned L1, but only one trial (NCT05348278, Phase 2/3, status unknown) is a Phase 2/3 RCT, and no Phase 3 trial of urea has a confirmed completed result. Under the stated rules this fits L2 better, so L2 is used here. The Phase 3 trials with urea arms (NCT02251392 is unknown status; NCT02247830 is completed, n=48, and is small).
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available. Based on known information, urea is a well-established topical humectant, keratolytic and skin-barrier-enhancing agent. It is a natural component of the skin's moisturising factor and increases stratum corneum hydration. The reviews compiled for this report also describe regulation of keratinocyte differentiation and antimicrobial peptide gene expression.
Dermatitis is already covered by the original indications (atopic, contact, seborrheic and occupational dermatitis), so this prediction is largely on-label. The newer, more specific signals are in treatment-related skin injury: radiodermatitis in breast and head-and-neck cancer patients, and hand-foot skin reaction from capecitabine. In these settings, barrier support and hydration are plausible ways to reduce skin damage.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT05348278 | Phase 2/3 | Unknown | 214 | Urea-based cream to prevent capecitabine-associated hand-foot skin reaction; an earlier study was negative, and this one looks beyond the first cycle |
| NCT03901144 | Phase 2 | Completed | 50 | Novel moisturiser in atopic dermatitis, measuring skin barrier effect (urea likely in comparator or test arms) |
| NCT06553417 | NA | Completed | 60 | Emollient "plus" compared with urea 10% in mild-moderate atopic dermatitis |
| NCT05939726 | NA (Phase II RCT) | Completed | 145 | Moisturising creams with or without vitamin E added to urea-based cream, or urea cream alone, in capecitabine-associated palmar-plantar erythrodysesthesia |
| NCT02249884 | Phase 2 | Completed | 30 | Chamomile gel and urea cream for radiodermatitis; dose-finding |
| NCT02251392 | Phase 3 | Unknown | 100 | Chamomile gel, chamomile infusion and urea in radiodermatitis |
| NCT02247830 | Phase 3 | Completed | 48 | Chamomile gel or urea cream to prevent radiodermatitis versus usual care |
| NCT05641246 | Phase 2 | Completed | 86 | Urea-based cream plus topical diclofenac for hand-foot syndrome in breast cancer patients on capecitabine |
| NCT00576238 | Phase 3 | Completed | 55 | Betamethasone cream tolerance and moisturiser effect on eczema recurrence; urea involvement unclear |
| NCT00771121 | Phase 4 | Unknown | Not reported | Moisturising creams and skin barrier function; indirect support only |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 28166390 | 2017 | Systematic review (Cochrane) | Cochrane Database Syst Rev | Emollients and moisturisers for eczema; moisturisation is an integral part of treatment |
| 34596890 | 2021 | Review | Dermatol Ther (Heidelb) | Urea's emollient, moisturising, keratolytic, barrier-enhancing and antimicrobial properties |
| 30378232 | 2018 | Review | Dermatol Ther | Clinical evidence for topical urea in healthy skin and skin disorders including atopic dermatitis |
| 40265493 | 2025 | Review | Int J Dermatol | Basic emollients (including urea) for xerosis in atopic dermatitis |
| 40231699 | 2025 | Review | Int J Dermatol | Mechanisms of skin hydration and how basic emollients restore barrier function |
| 14572299 | 2003 | Review | Am J Clin Dermatol | Emollients and moisturisers in dry skin barrier disorders, including atopic skin and contact dermatitis |
| 39973079 | 2025 | Clinical study | J Cosmet Dermatol | Emollient "plus" compared with urea 10% in mild-to-moderate atopic dermatitis |
| 35167133 | 2022 | Clinical study | Clin Exp Dermatol | Different emollient creams have varied effects on skin barrier in adults with atopic dermatitis |
Singapore Market Information
The Singapore licences do not list approved indication text. All four are single-ingredient topical creams with valid status.
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN10864P | AXCEL UREA CREAM 10% w/w | Cream | Not stated |
| SIN08347P | U O CREAM 10% | Cream | Not stated |
| SIN08726P | UCORT CREAM | Cream | Not stated |
| SIN02881P | HYDROCORTISONE 1% ET UREA 5% CREAM | Cream | Not stated |
Safety Considerations
- Contraindications (knowledge-graph signal, not label text): Purulent otitis media, ear infection and otitis media.
- Drug Interactions: 54 interactions are recorded, all of those listed being Moderate level. Main ones include:
- Laxatives and bowel-preparation agents (bisacodyl, picosulfuric acid, polyethylene glycol, sodium sulfate, lactulose, lactitol, magnesium hydroxide, magnesium citrate, glycerin, castor oil, mineral oil, phenolphthalein)
- SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin, ertugliflozin)
- Exenatide, sibutramine and iothalamic acid
These are largely relevant to systemic exposure, and the practical significance for topical use is likely low but should be confirmed.
For warnings and contraindications from the label, please refer to the package insert, which was not available for this report.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Urea is already marketed in Singapore as topical creams, and dermatitis overlaps with its established uses. Supporting trials exist, notably in radiodermatitis and capecitabine-related hand-foot reactions. However, several of the key trials are of unknown status, small, or have urea only as a comparator, and the one earlier capecitabine study was negative. The evidence is supportive but not definitive.
To proceed, the following is needed:
- Package insert warnings and contraindications from HSA (currently missing; this blocks formal safety screening)
- Approved indication text for the Singapore licences
- Detailed mechanism of action data from DrugBank
- Confirmed results of NCT05348278, NCT05939726 and the radiodermatitis trials
- Review of the otitis-related contraindication signal and guidance on use in neonates, infants and damaged skin
- Note that the other nine predictions (for example acne keloid, dermatomyositis, interstitial lung disease) have no supporting trials and are best held as model predictions only. Acne (disease) has indirect evidence only, from one benzoyl peroxide in 10% urea vehicle study.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.